A study from Fred Hutchinson Cancer Research Center, the University of Alberta, Canada and in Ankara, Turkey has found that for women whose diet is already high in folic acid, adding a folic acid supplement weakens the immune system. The women’s natural killer cells function fell below that of women deficient in folate who were not taking any supplement.

“Folic acid (FA) supplements and food fortification are used to prevent neural tube defects and to lower plasma homocysteine,” the authors point out. “Through exposure to food fortification and vitamin supplement use, large populations in the United States and elsewhere have an unprecedented high FA intake.”

The researchers evaluated dietary and supplemental intakes of folate and FA “in relation to an index of immune function, natural killer cell (NK) cytotoxicity, among 105 healthy, postmenopausal women.” What they found is surprising.

“Among women with a diet low in folate (<233 µg/d), those who used FA-containing supplements had significantly greater NK cytotoxicity…. However, those who consumed a folate-rich diet and in addition used FA supplements > 400 µg/d had reduced NK cytotoxicity compared with those consuming a low-folate diet and no supplements ….”

“Prompted by this observation, we assessed the presence of unmetabolized FA in plasma as a biochemical marker of excess FA. Unmetabolized folic acid was detected in 78% of plasma samples from fasting participants. We found an inverse relation between the presence of unmetabolized FA in plasma and NK cytotoxicity. NK cytotoxicity was ~23% lower among women with detectable folic acid ….”

This inverse relation was stronger among women 60 years or older. And the more unmetabolized FA concentrations in the women’s blood, the weaker the natural killer cells.

“Because of the increased intake of FA in many countries,” the authors conclude, “our findings highlight the need for further studies on the effect of long-term high FA intake on immune function and health.”

This study was published in American Society for Nutrition J. Nutr. 136:189-194, January 2006.
Abstract and full study are online:
Unmetabolized Folic Acid in Plasma Is Associated with Reduced Natural Killer Cell Cytotoxicity among Postmenopausal Women — Troen et al. 136 (1): 189 — Journal of Nutrition

For a Dietary Supplement Fact Sheet: Folate go to NIH Office of Dietary Supplements.